We propose to commercialize a high-speed instrument for automated DNA sequence analysis. Such an instrument is essential to the success of the Human Genome Initiative, in which the sequence of the human genome will be determined and used as a powerful tool for biological and medical research. Two key aspects of this project will be addressed; the development of exceptional new fluorescent reagents, and a commercially viable instrument. In phase one we will test superior fluorescent reagents and optimize them for use in high-speed automated DNA sequencing. This will involve coupling all candidate fluorophores to primers and testing for emission sensitivity, DNA synthesis efficiency and instrument compatibility. In phase two we will develop and commercialize an instrument capable of sequencing up to 26,000 bases/hour. This will be accomplished in collaboration with Dr. Lloyd Smith as he applies straightforward improvements to his current 8,000 bases/hour automated DNA sequencer as part of his ongoing research project. By commercializing innovations derived from federally funded research and stimulating additional innovations in fluorophore research, an automated DNA sequencer with twenty fold greater throughput than any now on the market will be available to the U.S. Human Genome project by September 1995.